The overall objectives of the proposed research are to define in molecular terms the initial biochemical and physiological responses of the neutrophil to chemotactic agents and to investigate the nature and role of activatable esterases (proteases) in the neutrophil and other cells. To this end we propose to study the structure activity relationships of formylmethionyl peptide for neutrophils, isolate the formylmethionyl peptide receptor and prepare antibodies to it. The calcium requirements for chemotactic peptide induced granule enzyme secretion and stimulated orientation and locomotion of neutrophils will be further studied. The role and nature of arachidonic acid metabolites involved in granule enzyme secretion in neutrophils will be studied using 14C-arachidonic acid followed by identification and isolation of metabolites. The role of neutrophil esterase-activation in phospholipase activation and production of arachidonic acid is to be investigated in neutrophils using the same approach employed for platelets. Antibodies to the purified chymotrypsin-like esterase of rabbit peritoneal neutrophils will be prepared and used to localize the enzyme in the cell. The substrate specificity of the esterase activated during the antigen-antibody induced locomotion of B lymphocytes will be studied using radioactive benzoyl L arginine methyl ester and protein substrates. Additionally, we shall seek evidence that the stimulus specific esterases activited during platelet serotonin release are the same as those that aid phospholipase activation in the same cell.